Although gastric cancer mortality rates are gradually decreasing around the world, there are countries, especially in East Asia in which this disease remains prevalent. Helicobacter pylori colonization has been strongly associated with gastric cancer in cohort and case-control studies. Until now, most studies have reported an association between H. pylori and gastric cancer using serological surveys with pools of cell surface preparations from the bacteria as the antigen. However, H. pylori isolates from different geographic areas vary in genotype. We propose to design specific antigenic regions from the major virulence marker of H. pylori (VacA), and by assessing the immune response to this bacterial antigen, determine whether it is a better predictor for the risk of development of gastric cancer in selected populations. For VacA we will obtain peptide antigens specific for the mid region (m1 and m2) because preliminary data suggests that differences in this region may be a predictor of the development of gastric cancer. From a nested case-control study of Japanese-Americans in Hawaii, serum samples were obtained from individuals before they developed gastric cancer over a 21-year follow-up. We also have serum samples from control individuals who did not develop gastric cancer. We expect to find that the immune response to one particular vacA genotype (m1) is predominantly observed in those patients who developed gastric cancer compared to those in whom gastric cancer did not develop. If our hypothesis is correct, we hope to establish a simple and economical serological test to assess the risk of gastric cancer development.